Inject

HANDBOOK OF PHARMACEUTICAL
GENERIC DEVELOPMENT

St e r i l e
Inj ect i ons

VOLUME 20 - Part One
Dr ug Devel opment - St er i l e I nj ect i ons

GENERI C DEVELOPMENT
H a n d b o o k o f P h a r m a c e u t i c a l
G e n e r i c D e v e l o p m e n t S e r i e s
Sterile Dosage Form Generic Drug Development Series

24 VOLUME DRUG DEVELOPMENT SERIES PRODUCT DEVELOPMENT
SERIAL NUMBER - DO NO REMOVE! - REGISTERED WITH

34004357-09
LOCUM INTERNATIONAL PUBLISHERS REGISTRATION SERVICES
WARNING: THIS ISSUE A IS MULTIPLE PAGE UV ENCODED EDITION.
HPGD 24 Vol. SERIES STERILE INJECTIONS - Part I
First & Second Int. Edition - 01 & 02 (First & second print run) Published 1995/6/7/8.
Third International Edition - 03 (1
st
, 2
nd
and 3
rd
printing) - Published 1999/2000/2001.
Forth International Edition - 04 (First & second print) - Jan / July 2002 & 2003.
Fifth International Edition - 05 (1
st
International Printing) - Publishing Date - January 2004
Sixth International Edition - 06 (1
st
Edition Printing) - Publishing Date - May 2005
Published and distributed in UK, US, EU, Israel, Asia, and Japan in by Locum International
Publishing House (Houston, Israel, South Africa) in Soft and Spiral Cover; and Electronic CD
ROM. All print and electronic editions are identical in content & format.
Seventh International Edition - 07 (1
st
International Printing) - Publishing Date-January 2006
Eighth International Edition - 08 (1
st
Ninth International Edition - 09 (1
st
Tenth International Edition - 10 (1
st
Copyright 1995 Handbook of Pharmaceutical Generic Development. Text Copyright
1995 Handbook of Pharmaceutical Generic Development. Illustration copyright 1995
Handbook of Pharmaceutical Generic Development. Locum International Group Publishing
House 562 Monaco L Delray Beach Florida 33446-1938 USA-All rights reserved.
ISSN 0793 8659
ISSN 0793 8667 - Electronic Version (Online, CD ROM and e-mail PDF versions)

Handbook Development 24 volume series General Generic Development ISSN Series
number 0793 7407 General Generic Development ISSN Series number 0793 7792 -
Electronic Issue (Online and CD ROM are identical in size and content to the printed hard or
soft cover version.)
Duplication: No part of this publication may be reproduced, stored in a retrieval
system or transmitted in any form or by any means, electronic, mechanical,
photocopying, microfilming, recording or otherwise, without the prior written
permission of the copyright owner or subject to the following conditions:
Authorization to photocopy items for internal or personal use or internal or personal
use of specific company personnel is granted by Locum International Publishing
House, provided that the base fee of $1 per page is paid directly to the Copyright
Clearance Center (CCC) 222 Rosewood Drive, Danvers, MA 01923 USA. For
organizations that have been granted a photocopy license by CCC, a separate
system of payment has been arranged.
For additional information, contact the Publications Department Locum International
Publishing House, PO Box 874, 50 Gilad Street, Kochav Yair, 44864 Israel.

Canada Fax: + (1) 561-495 0585
US Fax: + (1) 561-431 2620
EU Fax: + 972 97-494 532
Global Orders Fax: + 972 3-725-5751
E-mail: info@locum. co. il
ht t p: / / www. l oc um. c o. i l
ht t p: / / www. l oc umeur o. c om
ht t p: / / www. l oc umusa. c om
info@l oc umUSA. com
info@l oc umEur o. com

Current Printing (last digit): 10 9 8 7 6 5
PRINTED IN USA
PRINTED IN ISRAEL
PRINTED IN IRELAND
PRINTED IN REPUBLIC OF SOUTH AFRICA


Pa r t One
S t e r i l e
Injections

Drug Devel opment

Locum International Publishers
Handbook o f
Pharmaceutical
G e n e r i c
Development

Copyright LIG - Locum Publishing
House Inc. All Rights Reserved.
Neither this book nor any part may be
reproduced or transmitted in any form or
by any means, electronic or mechanical,
including photocopying, microfilming and
recording, or by any information storage
and retrieval system, without the
permission of the publishers.

BLOCK J D & BELLE D

The Complete Handbook Ser i es o f
Ph a r ma c e u t i c a l Dr u g De v e l o p me n t
ISBN 0793 8632 - Electronic Version - Handbook Development 24 Volume Series
ISSN Series Number 0793 761X - Electronic Version.

Handbook of Pharmaceutical Generic Development
Part I (Development) & Part II (Formulation -Development/ANDA)
Vol. 1
Tablets IR Oral
Part I (Development) & Part II (Formulation - Development/ANDA)
Vol..2
Capsules IR Oral
Vol. 3
Semisolids Topical
VOL. 4
Liquids Oral
Part I (Development) & Part II (Formulation-Development/ANDA)
VOL. 5
Soft Gelatin Capsules
VOL. 6
e-SOPs / SOPs
Part I (Development) & Part II (Formulation-Processes & ANDA)
VOL. 7
Suspensions IR Oral
Standard & Reconstituted
VOL. 8
Sterile Eye Preparations
VOL. 9
Nasal Preparations
Part I (Development) & Part II (Formulation ; Processes & ANDA)
VOL. 10
Oral Tablets CR / MR
VOL. 11
Oral Capsules ER
VOL. 12
Oral EC Tablets DR
Part I (Method Validation) & Part II (Analytical Methods 1994-2008)
VOL. 13
S I Assays HPLC
75 Stability Indicating Assays
Handbook of Pharmaceutical INNOVATIVE Development
VOL. 14
Tablets IR Oral
VOL. 15
Capsules IR Oral
VOL. 16
Suspensions IR Oral
Handbook of Pharmaceutical DRUG Development
(TITLE 17 SERIES Master Formula & Process Instructions)
VOL. 17
MF & MMI Parts 1 - 5
(TITLE 17 SERIES Master Formula & Process Instructions)
VOL. 18
MF & MMI Parts 6 - 10
Part I, II & III (Development, Manufacturing & Engineering
VOL. 19
SOPs / PAI-Checklist
Part I (Development) & Part II (Formulation ; Development &
ANDA)
VOL. 20
STERILE INJECTIONS
Part I (Development) & Part II (Formulation ; Processes & ANDA)
VOL. 21
Chewable IR Tablets

Available either as Soft Bound, Soft Spiral Cover (for Updating) or CD ROM.
Additional Drug Specific Volumes in Preparation. An on-going electronic and print series

For Drug Specific Handbooks refer to the 120+ Drug Development Series titled

READY-TO-GO DRUG DEVELOPMENT SERIES
http://www.locumusa.com/2go/gocmc
O http://www.iagim.org O



Acknowledgments

I.A.G.I.M. (R&D) Foundation.
I.A.G.I.M. Research Council.
Contributions - Generic & Research Firms
Associate Universities, Technicons and Consultants.
Handbook Series Coordinating Committee.
International Journal of Drug Development.
International Journal of Drug Formulation.
Journal of Pharmaceutical Development.
International Journal of Generic Drugs.
International Journal of Drug R&D
I.A.G.I.M. Drug Development Archives
Locum International Archives.
FDA/OGD/CDER Maryland
Guides and Guidelines
Library of Congress.
AIC Conferences.
Editorial Board.
Pharm. Eur.
USP/NF.
USPC.
BP.
=

To Dor i bel l e
f or her y ear s of s uppor t and hel p
to Sean for his expert knowledge on computerization
to David and Ari for running the project's computers
and lastly to Pat for his inestimable
contribution.

24 Volume Series
International Edition

L O C U M P U B L I S H I N G H O U S E
j = )
g Locum Press _
j = )


EDI TOR' S NOTE
Handbook of Generic Development Series - Sterile Injections
This handbook represents the current International Edition of the ongoing 24 volume
series of Generic Drug Development and appears under the cumulative title of the
Handbook series of Generic Drug Development. The ongoing series is updated
annually at the end of each year. This is an ongoing process as new data,
specifications and process techniques are added on a continual and expanding
basis. This handbook is fact never fully complete, as each new annual edition brings
an enlarged and extended profile in the drug development process, as well as new
agency rules, guidelines and guidance to industry which continues year by year as
the global product data base expands. Over 150 scientific publications and drug
development conferences are annually referenced in the 48 volume Handbook series
of Generic Drug Development.
This mammoth task presents a continual ongoing commitment to the improvement of
the technical databases and the product specific drug development requirements and
know-how through the world wide IAGIM joint ventures and know-how projects
currently active in over 15 countries.
The Handbook is available in electronic format (Online and CD ROM) and the e-
format is up-dated annually to Association Members of IAGIM.
This current international edition of the Handbook has been redesigned and updated
to meet the current Guidance for Industry - Organization of an Abbreviated New Drug
Application and an Abbreviated Antibiotic Application as well as all current approved
and key draft FDA guideline requirements of the Center of Drug Evaluation and
Research (CDER) up to current date. Editor-in-chief

/)
International Edition
OLOCUM=PRESSO
World wide distribution
COPYRIGHT
All Rights Reserved
g<_

ISSN 0793 8632
An o n - g o i n g s e r i e s

Ad d i t i o n a l Vo l u me s i n P r e p a r a t i o n
General Drug Development Series ISSN 0973 7601
Electronic Drug Development Series ISSN 0973 761X

/)
COPYRIGHT LOCUM Int.
Og<_O
Table of Contents.
Handbook of Pharmaceutical i Generic Development
CONTENTS
PHARMACEUTI CAL DEVEL OPMENT
Table of Contents VIII
Acronyms - Abbreviations XIII
Introduction XV
Preface XVI
Forward XVII
Chapter 1
Regulatory 1.1
- Pre-formulation checklist 1.3
Documentation 1.4
- SOP Control checklist 1.6
Development Notebooks 1.7
- Development Notebooks checklist 1.9
- SOP Control and Development Notebooks SOPs 1.10
Chapter 2
Developing the Formula -an Overview 2.1
- Formulation checklist 2.2
- Development formulations - sterile preparations 2.3
Drug Development Checklist 2.5
Development Formula SOPs 2.6
Developing Sterile Formulations 2.7
Design Considerations for Sterile Formulations 2.12
Product Development data - Case Histories 2.13
Product Development Guide and tabulations 2.21
Product Development Flowchart 2.27
Developing Sterile Preparations 2.29
Sterile Formulations Master Formulations 2.35
Purified Water - an essential ingredient 2.33
Development - Paclitaxel 2.38
Purified Water - Checklist 2.46
Aseptic processing guidelines 2.54
Chapter 3
Active Ingredients 3.1
-Dos and Donts 3.2
-Active checklist 3.3
-Approved Suppliers Checklist 3.5
-Alternative API Suppliers - Actives 3.7
Table of Contents.
Handbook of Pharmaceutical ii Generic Development
Contents
Chapter 4
Semi active ingredients 4.1
-Validating the Semi-active ingredients, Checklist 4.2
Non active materials (excipients) 4.3
-Checklist non active ingredient 4.5
-Standard Operating Procedures, Non actives 4.6
Chapter 5
Container closure systems 5.1
-Container-closure systems, Checklist 5.3
-Container-closure systems, SOPs 5.4
-Packaging Components - Documentation Requirements 5.5
-Packaging Components - Description and Characteristics 5.11
-Packaging Components Documentation Requirements SOP 5.12
-Packaging Components - Compendial Test Requirements 5.16
Chapter 6
Manufacturing Instructions & in-process controls 6.1
Production In-process controls 6.2
Quality Control In-process Testing Schedule 6.4
- Manufacturing & Controls - Sampling procedures 6.6
- The manufacturing Instructions and Controls 6.10
- Manufacturing Flow Charts 6.23
- Fill Weight Verification 6.20
- Fill Weight Verification Tabulations 6.33
- Packaging trail and Disbursements 6.35
Chapter 7
In-process Quality Controls 7.1
-Manufacturing in-process controls; Checklist 7.2
-In-process Quality Controls; SOPs 7.5
Chapter 8
Finished Product Specifications 8.1
- Finished Product Specifications example and Checklist 8.2
- release Specifications 8.4
- Glossary and Terms 8.9
- Finished Product Specifications; Required SOPs 8.12
Table of Contents.
Handbook of Pharmaceutical iii Generic Development
Contents
Chapter 9
Process Optimization and Procedures 9.1
Evaluation Product Specifications 9.3
Qualification of Preservative and Chelating Agent 9.4
Qualification of Preservative and Chelating Agent - Stability studies 9.6
Chapter 10
Scale-up Procedures 10.1
- Scale-up procedures; checklist 10.4
- Scale-up procedures; SOPs 10.5
Chapter 11
Cleaning Limits 11.1
Cleaning Limits Procedures; Checklist 11.6
Cleaning Validation Requirements; SOPs 11.9
Chapter 12
Analytical Validation Requirements 12.1
-Analytical Testing Out of Specification 12.39
-Analytical Testing Outliers 12.48
-Out of Specification 12.49
-Impurities in Drug Substances 12.51
-Impurities Glossary of terms 12.62
-Impurities Do's and Don'ts 12.63
-Impurities Decision Trees 12.64
Analytical Post approval Changes -PAC-ALTS 12.67
PAC-ALTS Checklist 12.67
Chapter 13
Process Qualification Batch 13.1
-Process Qualification Batch; Checklist 13.2
-Process Qualification Batch; SOPs 13.3
-Process Qualification Blend Analysis 13.5
-Process Qualification Blend Analysis - Do's and Don'ts 13.7
-Ruggedness and Robustness 13.10
-Process Qualification - Qualifying Bulk Solutions - Protocol 13.14
Table of Contents.
Handbook of Pharmaceutical iv Generic Development
Contents
Chapter 14
Pivotal batch 14.1
-Pivotal batch Checklist 14.2
-Sampling and Testing the Pivotal Batch - solution reconstitution 14.5
-Auditing the Pivotal batch 14.11
-Auditing the Pivotal batch Checklist 14.13
Chapter 15
Exclusion of Biostudy Testing - Sterile Solutions 15.1
Chapter 16
Technical Transfer Documentation 16.1
TTD Contents 16.2
-Technical Transfer Documentation; checklist 16.5
-Technical Transfer Documentation; Pharmaceutical Part 16.7
-Technical Transfer Documentation; Analytical Part 16.10
Chapter 17
Process Validation Plan 17.1
-The Process Validation Batches; checklist 17.2
-Process Validation Requirements; SOPs 17.4
-Process Validation Master Plan 17.5
-Process Optimization Master Plan 17.7
-Process Validation, Stability and Statistics 17.8
-Validation Protocol - bulk sterile solutions17.14Validation Check List - 17.14
-Installation and operational qualification 17.18
-Prospective Validation Protocol - sterile Cefuroxime Sodium 17.32
-Prospective Validation Protocol - Lyophilized Vancomycin HCl 17.36
-Prospective Validation Protocol - Aciclovir Sodium for IV infusion 17.44
-Validation Check List - Purified water USP 17.48
-Validation Check List - WFI System 17.54
-Validation Check List - Pure Steam System 17.58
-Validation Check List - Compressed Air System 17.64
- Validation Check List -Washing Machine System 17.68
- Validation Check List - Sterile Nitrogen System 17.72
- Validation Check List - Autoclave 17.76
- Validation Check List - Dry heat Oven 17.82
- Validation Check List - Lyophilizer 17.88
- Validation Check List - Sterilizing Tunnel 17.92
- Validation Check List - Equipment and machines 17.96
- Validation Check List - HVAC System 17.99
Table of Contents.
Handbook of Pharmaceutical v Generic Development
Contents
Chapter 18
Pre--Approval Inspections & Failures 18.1
PAI Audits 18.5
PAI Mock Inspections 18.7
PAI Summary 18.8
Pre--Approval Inspection Audit - Team Set Up 18.9
Pre--Approval Inspection Audit - Team Activities 18.11
Chapter 19
Stability Testing of Drug Substance and Drug Product I 19.1
Stability Testing of Drug Substance and Drug Product II 19.15
Stability Testing of Drug Substance and Drug Product II 19.21
Stability Testing Significant Change 19.24
Storage Conditions 19.29
Setting up a functional Stability Unit 19.31
Stability SOPs Development 19.39
Chapter 20
Standard Operational Procedures
Development SOPs 20.1
Index of Pharmaceutical Standard Operating Procedures 20.5
Index of Analytical Standard Operating Procedures 20.9
Index of Microbiological Standard Operating Procedures 20.16
Index of Stability Standard Operating Procedures 20.21
ISSN 0793 8632
A n o n - g o i n g s e r i e s
A d d i t i o n a l V o l u me s i n P r e p a r a t i o n
ISBN 0793 8640 - Electronic Version
Handbook Development 24 Volume Series
ISSN Series Number 0793 7792 - Electronic Version
H a n d b o o k o f P h a r m a c e u t i c a l
G e n e r i c D e v e l o p m e n t S e r i e s
Table of Contents.
Handbook of Pharmaceutical vi Generic Development
H P G D
H a n d b o o k o f P h a r m a c e u t i c a l G e n e r i c D e v e l o p m e n t
Drug Development - Part I
ANDA Formula - Part II
Copyright 1995 -2004 Locum International Ltd.
2006-7 Update Program
Part I and Part I I : HandBook Generi c Devel opment Seri es
Initiation Date : January 2006
Expiration Date : January 2007
No of Years : One (1)
Update Period : January 2006 to January 2007.
This Drug Development ANDA has been updated to January 2006 Office of Generic Drugs
requirements. Handbook clients with multiple handbooks requiring to continue this annual service
need only to become members of I.A.G.I.M. for the period of the update service required by the firm.
The ANDA Update Program is renewed in December each year as a function of the firms
requirements. Standard Plan (one year) IAGIM members may purchase the update with the adjacent
form.
Warning: Copyright 1985 -2006 Locum Publishing House Inc. - All Rights Reserved.
Neither this information or nor any part of the data contained therein may be reproduced, copied or transmitted
in any form, modification or merged portion or by any means, electronic or mechanical, including printing
photocopying, microfilming and recording, or by any information storage and retrieval system, without the prior
written permission of the publishers. Trademark - Locum Corporation, Locum International
Group
info@locumusa.com
(See web site for IAGIM Application Membership form)
i n f o @l o c u mG r o u p . o r g
http://www.locumGroup.org
Update License No:
1.3.02-000

Inject

Hochgeladen von

Dokumentinformationen

Originalbeschreibung:

Originaltitel

Copyright

Verfügbare Formate

Dieses Dokument teilen

Dokument teilen oder einbetten

Freigabeoptionen

Stufen Sie dieses Dokument als nützlich ein?

Sind diese Inhalte unangemessen?

Copyright:

Verfügbare Formate

Inject

Hochgeladen von

Copyright:

Verfügbare Formate

HANDBOOK OF PHARMACEUTICAL

Das könnte Ihnen auch gefallen